This invention relates to a method and materials that are designed for use in automating urinalysis. This system is designed to analyze urine for its constituents by a method that is fully automated (does not require the use of manual methods such as refractometer, pH meter, dipsticks, etc). Automation as designed by this system would be directed to the use of a self-operating instrument that is capable of handling multiple reagents designed for use on a automated analyzer system for the quantitative determination of Leukocytes, Blood, pH, specific gravity, Glucose, protein, Bacterial Nitrite, and Total Ketone Bodies in urine.
It is known that the most common method for the analysis of urine is by the use of a manual technique known as a dipstick. This method for the analysis of urine is labor, time intensive, and costly among other detriments. The use of a dipstick for analysis of urine also relies on the subjective interpretation of the technician. The dipstick method requires the technician to submerge the dipstick in a sample of urine and remove it. To wait a specified time, then compare the color development of the test on the dipstick to a color chart. Even more cumbersome methods involve the use of a refractometer, pH meter, or manual chemistry test. The automated urinalysis system offers a method for reducing the consumable materials, and labor costs. The system also offers increased accuracy, sensitivity, and objective quantifiable determinations of urinary constituents for better diagnostic interpretation of the test results of urine, thus enabling a physician to provide better health care for the patient.
In today's atmosphere of rising health care costs and the concomitant reduction in the quality care, a system for the determination of normal or disease state in urine that reduces the cost of testing by decreasing, time, labor, and cost of test materials is called for. An obvious advancement in the science of urinalysis would be to move it from the slow, tedious, and costly techniques such as the dipstick or other manual operations to a fully automateable system that would speed up turn-around-time of obtaining test results, shorten doctor office visits, and reduce overall health care costs. The automated urinalysis system enables a technician to take a sample of urine and place it on an auto analyzer that contains the system reagent materials for each of the above referenced tests, start the self-operating analyzer, and walk away to other duties until the results are reported by the analyzer. Most of the high throughput analyzers currently in use throughout the industry would allow testing in the aforementioned method of hundreds to thousands of urines per hour. This is a marked improvement when compared to manual techniques such as the dipstick which at best would take hours and several technicians to analyze a hundred specimens. An article printed in the American Journal of Clinical Pathology Vol. 83 pages 740-743, discusses the cost of using the dipstick as a screening test for urinalysis. The dipstick methodology can qualitatively determine normal urine constituents. This article states "The urine dipstick procedure costs approximately $0.76 for reagents and 3.0 minutes of the technologist's time". This equates to 20 samples per hour with the use of dipsticks. Another point to make here is that the cost has obviously risen since 1985. The time is now for the evolution of acceptable techniques for determining normal and abnormal urinary constituents.
The following list of assay devices utilizing prior art includes dry tablets, dipsticks, or other manual techniques for the analysis urinary constituents. None of the prior devices foresee or teach of a multiple/single liquid reagent system designed specifically for auto-analyzers to analyze urinary constituents quantitatively.
One such U.S. Pat. No. 4,147,514 discloses test strips (dipsticks) for the detection of ketone bodies. The assay strips are made up of a chemical bonded to a cellulose pad on a strip. This is then dipped into a specimen sample. This method only determines ketone bodies qualitatively at its best, due to inability of the system to allow the use of standards and controls on the same strip the sample is applied to. This assay does not foresee or teach of a liquid reagent system that is designed to be pumped by an autoanalyzer system into its discrete cuvette and there mixed with a urine sample, and then measured by spectrophotometric means, and followed by a computer driven calculation of a quantitative value derived from standards previously run by the same analyzer. By utilizing an objective instrument (autoanalyzer) which incorporates the use of standards and controls instead of the subjective observation of the naked human eye with no set reference point. The automated urinalysis system can elucidate scientifically verifiable increases in accuracy, precision, and sensitivity yielding quantitative reproducible results. The dipstick method can not accommodate the use of standards, or controls with every sampling of a urine for the calculation and verification of the result, and thus limits its utility to producing a qualitative result only. Nor, does the assay foresee or teach of the specific and unique chemical formulation that the automated urinalysis reagent for ketone bodies is comprised of. Obviously, many advances and differences exist between the automated urinalysis system (herein described) and the prior art. This automated system is a marked advancement in the art of urinalysis.
Another such patent, U.S. Pat. No. 3,146,070 discloses analytical compositions in dry form on a bibulous carrier (dipstick) impregnated with a pH indicator for the determination of pH. This assay at best only determines pH qualitatively, due to the inability to use standards and controls located on the same strip for the same test sample to define and verify a quantitative determination. The assay does not foresee or teach of a liquid reagent system that is designed to be pumped through an auto-analyzer, mixed with urine in a discrete cuvette, measured by spectrophotometric means, and automatically calculate a quantitative value derived from standards run previously on the analyzer. This system also allows for controls to be run periodically to insure continued precision of results. The dipstick method can not accommodate the use of standards or controls with every sampling of a urine for the calculation and verification of result, and thus limits its utility to producing a qualitative result with much less accuracy and precision than the automated urinalysis system. As mentioned and to further illustrate, the dipstick does not have the ability to sample a standard and the unknown solution at the same time, and on the same dipstick, and thus allow determination of a quantitative result. Nor does the assay foresee or teach of the specific and unique chemical formulation that the automated urinalysis reagent for pH is comprised of. Obviously there lies multiple advances and differences that exist between the automated urinalysis system and the prior art. This automated system exhibits a clear, obvious, and marked advancement in the art of urinalysis.
Additionally U.S. Pat. No. 4,318,709 discloses a device comprising a carrier matrix (dipstick) impregnated with the test means for specific gravity. This assay at best only determines specific gravity qualitatively, due to the inability to use standards and controls located on the same strip for the same test specimen. The prior art in this case also did not foresee the wide specimen to specimen matrix variations of real world urine samples including matrix components such as pH, and ionic strength, and the concomitant requirement of a multiple reagent system to effectively analyze urine for specific gravity in a liquid to liquid reaction. The normal pH value for urine can range from 4.5 to 8.0, which if using the prior dipstick method the results would be vastly scattered and inaccurate without a reagent to neutralize the effect prior to completion of the assay. The assay does not foresee or teach of a liquid reagent system that is designed to be pumped through an autoanalyzer, mixed with urine in a discrete cuvette, and measured by spectrophotometric means, and automatically calculate a quantitative value derived from standards previously run on the analyzer. The dipstick method does not have a means for the use of standards or controls with every sampling of a urine for the calculation and verification of a result, and thus limits its utility to producing a qualitative result with less accuracy and precision than the automated urinalysis system. As mentioned and to further illustrate, the dipstick does not have the ability to sample a standard and unknown solution at the same time, and on the same dipstick, and thus allow determination of a quantitative result. Nor, does the assay foresee or teach of the specific and unique chemical formulation that the automated urinalysis reagent for specific gravity is comprised of. Obviously there lies multiple advances and differences that exist between the automated urinalysis system and the prior art. This automated system exhibits a clear, obvious, and marked advancement in the art of urinalysis.
Various devices are described in the literature for the determination of particular urinary constituents one by one with the use of carrier matrices (dipstick, microcapusules, filter paper, etc.). None of the prior art teaches or elucidates a means for determining by automated technology urinary constituents from a single sample of urine, via multiple tests that are reported simultaneously by an autoanalyser using liquid reagents specifically designed for this family of instruments. As cited by the prior art, (in package insert literature) when evaluating laboratory test results, definitive diagnostic, or therapeutic decisions should not be based on any single result or method. However, the prior art states that dipsticks are affected by substances that cause abnormal urine color, such as drugs containing azo dyes (e.g., Pyridium, Azo Gantrisin, Azo Gantanol), nitrofurantoin (Macrodantin, Furadantin), and riboflavin, and thus may affect the readability of reagent areas on the urinalysis reagent strips (dipsticks). The color development on the reagent pad may be masked, or a color reaction may be produced on the pad that could be interpreted visually and/or instrumentally as a false positive or negative. This illustrates the susceptibility of the prior art to erroneous results due to misinterpretation of the color changes (due to subjective observation by analyst), or interference with the reagent color by urinary constituents that yield contradictory color changes, or contamination from adjacent reaction pads spilling interfering color and/or chemicals onto neighboring pads thus causing erroneous results (from cross reaction, inhibition, or activation with test reagents impregnated on test pads). Prior art does not envision or describe the unique formulations needed for such analysis. Furthermore, the prior art does not teach, describe, or elucidate, about a liquid reagent system designed for liquid to liquid reactions without the use of a carrier matrix. Finally, the prior art does not describe, teach, or elucidate, any knowledge of this automated urinalysis system that is capable of the analyzing unknown urine test samples at the same time as standards and controls to allow for the extrapolation of accurate, and reproducible quantitative values, yielding increases in accuracy, precision, and sensitivity. Therefore, it is considered highly desirable to provide a sensitive, rapid, accurate, reliable, time and cost saving, method and device for the determination of urinary constituents. None of the prior art known to the present inventors at the time of filing of the application teaches or suggests the invention presently disclosed and claimed.